[Relationship Between ABO Blood Group and Pregnancy Complications].

ABO blood group system is the most commonly used blood group classification system in clinic practice. The relevant antigens, A, B and H determinants, are complex carbohydrate molecules that are expressed in red blood cells and other cell lines and tissues. These antigens are determined by the ABO locus located on chromosome 9 (9q34.1-q34.2). ABO blood group is associated with the development of many human diseases, e.g., cardiovascular diseases, infectious diseases, and tumors. The relationship between the ABO blood group of pregnant women and various pregnancy complications, including preeclampsia (PE) and the related diseases, pregnancy associated venous thromboembolism (PA-VTE), gestational diabetes mellitus (GDM), and postpartum hemorrhage (PPH), have become the focus of obstetricians' recent research interest. Herein, we reviewed the relationship between ABO blood group and these pregnancy complications, and found that most of the reported findings supported the following views: 1) Blood type O is a protective factor for PE, while blood type AB increases the risk of PE; 2) blood types other than O are more prone to PA-VTE than blood type O; 3) blood type O or blood type AB may be related to the pathogenesis of GDM; 4) women of blood type O are at higher risks for PPH than those of other blood types. More in-depth epidemiological and genetic studies are needed to confirm these findings in the future. These findings can provide new ideas for researching into the pathogenesis of obstetric diseases and form the theoretical basis for obstetricians to prevent and treat related diseases.

Advance of sporadic Alzheimer's disease animal models.

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In the past decades, numbers of promising drug candidates showed significant anti-AD effects in preclinical studies but failed in clinical trials. One of the major reasons might be the limitation of appropriate animal models for evaluating anti-AD drugs. More than 95% of AD cases are sporadic AD (sAD). However, the anti-AD drug candidates were mainly tested in the familial AD (fAD) animal models. The diversity between the sAD and fAD might lead to a high failure rate during the development of anti-AD drugs. Therefore, an ideal sAD animal model is urgently needed for the development of anti-AD drugs. Here, we summarized the available sAD animal models, including their methodology, pathologic features, and potential underlying mechanisms. The limitations of these sAD animal models and future trends in the field were also discussed.

A review on the hybrids of hydroxycinnamic acid as multi-target-directed ligands against Alzheimer's disease.

Alzheimer's disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aß) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids, including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD.

Cinnamic Acid Derivatives: Recent Discoveries and Development Strategies for Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline and memory impairment. It is characterized by the accumulation of Amyloid-beta (Aß) plaques, the abnormal phosphorylation of tau protein forming neurofibrillary tangles, and is often accompanied by neuroinflammation and oxidative stress, which contribute to neuronal loss and brain atrophy. At present, clinical anti-AD drugs are mostly single-target, improving the cognitive ability of AD patients, but failing to effectively slow down the progression of AD. Therefore, research on effective multi-target drugs for AD has become an urgent problem to address. The main derivatives of hydroxycinnamic acid, caffeic acid, and ferulic acid, are widely present in nature and have many pharmacological activities, such as antimicrobial, antioxidant, anti-inflammatory, neuroprotective, anti-Aß deposition, and so on. The occurrence and development of AD are often accompanied by pathologies, such as oxidative stress, neuroinflammation, and Aß deposition, suggesting that caffeic acid and ferulic acid can be used in the research on anti-AD drugs. Therefore, in this article, we have summarized the multi-target anti-AD derivatives based on caffeic acid and ferulic acid in recent years, and discussed the new design direction of cinnamic acid derivatives as backbone compounds. It is hoped that this review will provide some useful strategies for anti-AD drugs based on cinnamic acid derivatives.

The marine Penicillium sp. GGF16-1-2 metabolite dicitrinone G inhibits pancreatic angiogenesis by regulating the activation of NLRP3 inflammasome.

Citrinin derivatives have been found to have various pharmacological activities, such as anti-inflammatory, anti-tumor, and antioxidant effects. Dicitrinone G (DG) was a new citrinin dimer isolated from marine-derived fungus Penicillium sp. GGF 16-1-2 which has potential activity. Here, we aim to investigate whether DG has anti-pancreatic cancer activity. In xenograft tumor model, 2 × 106 BXPC-3 cells were injected into the hind flank of NU/NU nude mice by subcutaneously for 2 weeks followed by treating with DG (0.25, 0.5, 1 mg/kg) and 5-FU (30 mg/kg) for 4 weeks. Tumor volume and weight were measured, and the expression of CD31, IL-18, NLRP3, and Caspase-1 in tumor tissue were detected. In vitro, HUVECs were treated with conditioned medium (CM) derived from BXPC-3 cells, the effects of DG on angiogenesis were detected by tube formation and western blot analysis. In vivo studies showed that the tumor growth and angiogenesis were greatly suppressed. The tumor weight inhibition rates of DG and 5-FU groups were about 42.36%, 38.94%, 43.80%, and 31.88%. Furthermore, the expression of CD31 and Caspase-1 were decreased. In vitro, CM derived from BXPC-3 cells which treated with DG could inhibit the tube formation and expression of pro-angiogenic NICD in HUVECs. Our study suggests that DG could suppress angiogenesis via the NLRP3/IL-18 pathway and may have the potential to inhibit tumor development.

Aqueous extract of Amydrium sinense (Engl.) H. Li alleviates hepatic fibrosis by suppressing hepatic stellate cell activation through inhibiting Stat3 signaling.

Background: The present study aimed to investigate the protective effect of the water extract of Amydrium sinense (Engl.) H. Li (ASWE) against hepatic fibrosis (HF) and clarify the underlying mechanism. Methods: The chemical components of ASWE were analysed by a Q-Orbitrap high-resolution mass spectrometer. In our study, an in vivo hepatic fibrosis mouse model was established via an intraperitoneal injection of olive oil containing 20% CCl4. In vitro experiments were conducted using a hepatic stellate cell line (HSC-T6) and RAW 264.7 cell line. A CCK-8 assay was performed to assess the cell viability of HSC-T6 and RAW264.7 cells treated with ASWE. Immunofluorescence staining was used to examine the intracellular localization of signal transducer and activator of transcription 3 (Stat3). Stat3 was overexpressed to analyse the role of Stat3 in the effect of ASWE on HF. Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that candidate targets of ASWE, associated with protective effects against hepatic fibrosis, were related to inflammation response. ASWE ameliorated CCl4-induced liver pathological damage and reduced the liver index and alanine transaminase (ALT) and aspartate transaminase (AST) levels. ASWE also decreased the serum levels of collagen Ⅰ (Col Ⅰ) and hydroxyproline (Hyp) in CCl4-treated mice. In addition, the expression of fibrosis markers, including α-SMA protein and Acta2, Col1a1, and Col3a1 mRNA, was downregulated by ASWE treatment in vivo. The expression of these fibrosis markers was also decreased by treatment with ASWE in HSC-T6 cells. Moreover, ASWE decreased the expression of inflammatory markers, including the Tnf-α, Il6 and Il1ß, in RAW264.7 cells. ASWE decreased the phosphorylation of Stat3 and total Stat3 expression and reduced the mRNA expression of the Stat3 gene in vivo and in vitro. ASWE also inhibited the nuclear shuttling of Stat3. Overexpression of Stat3 weakened the therapeutic effect of ASWE and accelerated the progression of HF. Conclusion: The results show that ASWE protects against CCl4-induced liver injury by suppressing fibrosis, inflammation, HSC activation and the Stat3 signaling pathway, which might lead to a new approach for preventing HF.

Clinical Features of Dermatomyositis/Polymyositis with Anti-MDA5 Antibody Positivity.

This paper aims to investigate the clinical and laboratory test characteristics of patients with anti-MDA5 antibody-positive PM/DM by analyzing the clinical characteristics, laboratory test results, and 1-year survival rate of patients with anti-MDA5 antibody-positive PM/DM in polymyositis (PM) and dermatomyositis (DM). To further investigate the impact of positive anti-MDA5 antibodies on the prognosis of PM/DM patients. According to the anti-MDA5 antibody test results, 18 cases with positive anti-MDA5 antibodies were in the positive group and 46 cases with negative anti-MDA5 antibodies were in the negative group. The clinical manifestations, laboratory tests, treatment protocols, and prognostic risk factors were collected for both groups. The chi-square test, Mann-Whitney method, Fisher test, t-test, Kaplan-Meier method, and Log-rank test were used for statistical analysis. Anti-MDA5 antibody positivity was more common in patients with DM/CADM. With no statistically significant differences in age and sex ratio between the two groups, The differences in erythrocyte sedimentation rate (ESR), ferritin (Fer), and creatine kinase (CK) levels in the positive group were statistically significant compared with the negative group. Clinically, the positive group was more prone to arthralgia, skin rash, and interstitial pneumonia.

Single cell RNA sequencing research in maternal fetal interface.

The maternal-fetal interface is an essential environment for embryonic growth and development, and a successful pregnancy depends on the dynamic balance of the microenvironment at the maternal-fetal interface. Single-cell sequencing, which unlike bulk sequencing that provides averaged data, is a robust method for interpreting the cellular and molecular landscape at single-cell resolution. With the support of single-cell sequencing, the issue of maternal-fetal interface heterogeneity during pregnancy has been more deeply elaborated and understood, which is important for a deeper understanding of physiological and pathological pregnancy. In this paper, we analyze the recent studies of single-cell transcriptomics in the maternal-fetal interface, and provide new directions for understanding and treating various pathological pregnancies.

PT109, a novel multi-kinase inhibitor suppresses glioblastoma multiforme through cell reprogramming: Involvement of PTBP1/PKM1/2 pathway.

Glioblastoma multiforme (GBM) is the most prevalent type and lethal form of primary malignant brain tumor, accounting for about 40-50% of intracranial tumors and without effective treatments now. Cell reprogramming is one of the emerging treatment approaches for GBM, which can reprogram glioblastomas into non-tumor cells to achieve therapeutic effects. However, anti-GBM drugs through reprogramming can only provide limited symptom relief, and cannot completely cure GBM. Here we showed that PT109, a novel multi-kinase inhibitor, suppressed GBM's proliferation, colony formation, migration and reprogramed GBM into oligodendrocytes. Analysis of quantitative proteomics data after PT109 administration of human GBM cells showed significant influence of energy metabolism, cell cycle, and immune system processes of GBM-associated protein. Metabolomics analysis showed that PT109 improved the aerobic respiration process in glioma cells. Meanwhile, we found that PT109 could significantly increase the ratio of Pyruvate kinase M1/2 (PKM1/2) by reducing the level of polypyrimidine tract-binding protein 1 (PTBP1). Altogether, this work developed a novel anti-GBM small molecule PT109, which reprogramed GBM into oligodendrocytes and changed the metabolic pattern of GBM through the PTBP1/PKM1/2 pathway, providing a new strategy for the development of anti-glioma drugs.

Recurrent and metastatic female adnexal tumor of probable Wolffian origin: A case report and review of the literature.

RATIONALE: Female adnexal tumors of probable Wolffian origin (FATWOs) are rare gynecologic neoplasms arising from the mesonephric duct remnants. Less than 90 cases have been reported in the English literature. Although most cases of FATWO are considered benign, recurrence and metastasis may occur in very few cases during the course of the disease. Due to the small number of recurrent and metastatic FATWO cases, there are no clear recommendations regarding optimal treatment. PATIENT CONCERNS: A 75-year-old postmenopausal woman, who underwent a mass excision of the right broad ligament three years ago, was found to have a right adnexal mass during a regular postoperative physical examination. DIAGNOSES: Vaginal ultrasound examination revealed a cystic and solid mass approximately 3.6 × 4.4 × 3.8 cm on the right side of the uterus. Three years ago, the mass of the right broad ligament was diagnosed with FATWO in the local hospital. Following extensive immunohistochemistry analysis and after reviewing the histology slides from the primary tumor, the final diagnosis of the mass on the right side of the uterus was recurrent and metastatic FATWO. INTERVENTIONS: The patient underwent laparoscopic mass excision, hysterectomy and resection of the metastatic lesion in the small intestine, and then she received 6 cycles of docetaxel and carboplatin-based chemotherapy. OUTCOMES: The disease has recurred three years after the first surgery in the local hospital. After the second surgery followed by systemic chemotherapy, there is no evidence of recurrence with 24 months of follow-up till now. LESSONS: FATWO is considered a benign entity. However, a few FATWOs have been shown to behave aggressively. Due to only a few reported cases, there are no comprehensive recommendations regarding the optimal clinical management of recurrent and metastatic FATWOs. Complete surgical resection followed by combination chemotherapy is considered to be the most effective therapy for recurrent and metastatic FATWOs. Chemotherapy with docetaxel plus carboplatin, which is most commonly used in malignant cases, may be effective in the treatment of recurrent and metastatic FATWOs.

Mesonephric adenocarcinomas in female genital tract: A case series.

ABSTRACT: Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients' clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.

A research update on the therapeutic potential of rhein and its derivatives.

Rhein is one of the anthraquinones components of Rheum. It shows excellent clinical efficacy and is widely used in the management of several disease conditions including tumors, inflammation, diabetic nephropathy, and viral infections. In this review, we summarize the recent studies on the pharmacological activities of rhein and its derivatives, as well as their association with different diseases and possible mechanisms based on our previous review. This review serves as an updated and a supplement to our previous report highlighting the use of rhein in nanotechnology. It also serves as a reference study and offers an overall picture of the use of rhein and its derivatives in nanotechnology.

Primary mesonephric adenocarcinoma of the fallopian tube: A case report.

BACKGROUND: Mesonephric adenocarcinoma (MNAC) is an extremely rare malignancy in the female genital tract. Only a few cases have been reported in the literature, and most of them occurred in the cervix, with extremely rare cases in the uterine body and ovary. MNAC has never been reported to arise in the fallopian tube. CASE SUMMARY: A 45-year-old woman was referred to our institution with a history of abdominal pain. Ultrasound revealed a cystic and solid mass in left adnexal region. The patient underwent complete staging surgery when intraoperative pathological examination demonstrated that the mass was malignant. The final histological and immunohistochemical results confirmed the diagnosis of MNAC originating from the fallopian tube. Then she received four cycles of combination chemotherapy with carboplatin plus paclitaxel. The tumor recurred with hepatic metastases 4 mo after initial surgery, and second resection of the tumors in the liver plus partial hepatectomy was performed. She was supplemented with five courses of a new combination chemotherapy with gemcitabine plus carboplatin, and there was no evidence of recurrence within the 22-mo follow-up period after the second surgery. CONCLUSION: MNAC originating from the fallopian tube is an extremely rare and high malignancy with a poor prognosis. It can be very aggressive, even at early stage. Little is known about the clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC originating from the fallopian tube. Herein we report the first case of primary MNAC deriving from the fallopian tube.

Mesonephric-like adenocarcinoma of the ovary: A case report and a review of the literature.

RATIONALE: Mesonephric-like adenocarcinoma (MLA) from ovary is a very rare tumor which derives from mesonephric duct remnant of the female genital tract. Only six cases have been reported so far in the English literature. PATIENT CONCERNS: A 29-year-old female patient was referred to the local hospital with a 20-day history of abdominal discomfort. DIAGNOSES: Pelvic ultrasound examination revealed a solid and cystic mass measuring 10 cm in diameter in the right adnexal area and a cystic mass measuring 5 cm in the left adnexal area. Postoperative pathology in the local hospital revealed suspected malignancy of the right ovary, and she was then transferred to our institution for definite diagnosis. The tumor mass was finally diagnosed as a primary MLA arising from the right ovary by histological and immunohistochemical examination in our institution. INTERVENTIONS: The patient underwent laparoscopic right adnexectomy and removal of left ovarian cyst in the local institution. Then, she underwent a complete staging surgery including a total hysterectomy, left adnexectomy, pelvic plus para-aortic lymphadenectomy, and omentectomy in our hospital. In addition, she received four cycles of combination chemotherapy with carboplatin plus paclitaxel. OUTCOMES: There is no evidence of recurrence with 13 months of follow-up till now, and we are still following-up this patient. LESSONS: MLA is an extremely uncommon malignancy with difficult diagnosis, unclear treatment and poor prognosis. Familiarizing with the clinical features and optimal management of this rare tumor may increase awareness of the disease among clinicians and pathologists, thus avoiding the misdiagnosis and mistreatment.

Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway.

Immunoglobulin A nephropathy (IgAN) is one of the most frequent kinds of primary glomerulonephritis characterized by IgA immune complexes deposition and glomerular proliferation. Zhen-wu-tang (ZWT), a well-known traditional Chinese formula has been reported to ameliorate various kidney diseases. However, its pharmacological mechanism remains unclear. Exosomes have been described in diverse renal diseases by mediating cellular communication but rarely in the IgAN. The purpose of the present study is to explore whether the underlying mechanisms of the effect of ZWT on IgAN is correlated to exosomes. Our results demonstrated that in human renal tubular epithelial cells (HK-2) stimulated by lipopolysaccharide, exosomes are obviously released after ZWT-containing serum treatment especially with 10% ZWT. In addition, once released, HK-2-derived exosomes were uptaked by human mesangial cells (HMC), which impeded the activation of NF-κB/NLRP3 signaling pathway to exert anti-inflammatory effects in a lipopolysaccharide induced proliferation model. Moreover, IgAN rat model was established by bovine serum albumin, CCL4 mixed solution and LPS. We found that 10% ZWT could significantly promote the release of exosomes from HK-2 and inhibit HMC proliferation to improve inflammation. Thus HK-2-derived exosomes treated with 10% ZWT (ZWT-EXO) were administered to the rats by tail vein injection. Our results showed that ZWT-EXO decreased the levels of 24 h proteinuria, urinary erythrocyte, IgA deposition in glomerulus and renal pathological injury which ameliorated the kidney damage. In addition, ZWT was able to dramatically promote secretion of exosomes in renal tissues while blocked NF-κB nuclear translocation as well as activation of NLRP3 inflammasome, leading to the inhibition of IL-1ß and caspase-1. In conclusion, our study reveal that ZWT has protective effects on IgAN by regulating exosomes secretion to inhibit the activation of NF-κB/NLRP3 pathway, thereby attenuating the renal dysfunction. These findings may provide a new therapeutic target for the treatment of IgAN.

Integrated Fecal Microbiome and Serum Metabolomics Analysis Reveals Abnormal Changes in Rats with Immunoglobulin A Nephropathy and the Intervention Effect of Zhen Wu Tang.

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.

Discovery of a novel small molecule PT109 with multi-targeted effects against Alzheimer's disease in vitro and in vivo.

Alzheimer's disease (AD), which is characterized by impairment of cognitive functions, is a chronic neurodegenerative disease that mainly affects the elderly. Currently available anti-AD drugs can only offer limited symptom-relieving effects. "One-compound-Multitargeted Strategy" have been recognized as the promising way to win the war against AD. Herein we report a potential anti-AD agent PT109 with multi-functions. First, an 81-kinase screening was carried out and results showed that PT109 potently inhibited c-Jun N-terminal kinases and Serum and glucocorticoid-inducible kinase 1, which are the important signaling molecules involved in neurogenesis, neuroprotection and neuroinflammation and mildly inhibit glycogen synthase kinase-3ß as well as protein kinase C gamma, both are involved in AD pathological processes. In addition, invitro studies of immunofluorescent staining and Western blot showed that PT109 might promote the neurogenesis of C17.2 cells and induce synaptogenesis in primary cultured rat hippocampal neurons. We detected and confirmed the neuroprotective effect of PT109 in cultured HT22 cells by MTT assay, dehydrogenase assay, glutathione assay and reactive oxygen species assay. Furthermore, the results of Western blot, ELISA assay and immunofluorescent staining indicated that PT109 attenuated lipopolysaccharide-induced inflammation in BV2 cells and primary astrocytes. The results of Morris water maze and Step-through test indicated that PT109 improved the spatial learning ability in APP/PS1 mice. More importantly, the invivo pharmacokinetic parameters indicated that PT109 had better medicinal properties. Taken together, our findings suggest that PT109 may be a promising candidate for treating AD through multiple targets although further studies are ought to be conducted.

Multi-targeted ChEI-copper chelating molecules as neuroprotective agents.

The identification of a valid therapeutic treatment for Alzheimer's disease (AD) represents nowadays an urgent and still unmet medical need, since currently available anti-AD drugs only relieve symptoms and show a modest efficacy. Recent evidence indicates that multi-target-directed ligands (MTDLs) can potentially provide an effective strategy to develop innovative therapies directed towards the onset and progression of this multifactorial neurodegenerative disorder. In this work we designed, synthesized and evaluated a new series of MTDLs bearing the rivastigmine skeleton (ChE-inhibitor) linked to known metal-chelating moieties with linkers of different length. For all the novel derivatives, AChE/BuChE inhibitory activity, ROS scavenging activity and potential cytotoxicity have been assessed. For the best compound (4), copper chelating properties and neuroprotective effects were also evaluated. Our data demonstrated that hybrid derivative 4 is able to effectively inhibit AChE and BuChE and to chelate copper, showing a protective action on neurons. These results, although preliminary, indicate that compound 4 can be considered as a possible hit molecule for the development of new anti-AD MTDLs.

Hyperthyroid heart disease in pregnancy: Retrospective analysis of a case series and review of the literature.

BACKGROUND: Hyperthyroidism in pregnancy may pose a great threat to maternal and fetal health. The risk of hyperthyroid heart disease (HHD), even heart failure, is significantly elevated in pregnant women. AIM: To investigate the clinical characteristics, prognosis, and therapy of HHD in pregnant women. METHODS: We searched the patient registry data at West China Second University Hospital of Sichuan University in Chengdu, China, following the approval by the Ethics Committee. We retrospectively analyzed the clinical characteristics of pregnant women diagnosed with HHD. The medical records of women with HHD during pregnancy from January 2012 to December 2017 were obtained from the electronic medical records system. All the included patients were followed in outpatient clinics and by telephone interviews until October 2018. RESULTS: A total of 155 patients were diagnosed with thyrotoxicosis, of whom six were diagnosed with HHD. Three of them had regular antenatal care. Two patients were complicated with acute heart failure attacks, and one of them had a stillbirth. Both of these patients had a long history of Graves' disease with poor treatment compliance. Treatments of precipitating factors such as the control of infection could relieve the symptoms and prolong gestation for a better prognosis. Hyperthyroid heart failure could be controlled with aggressive diuretics and management of the coexisting complications. Intense monitoring and timely anti-heart failure treatment were crucial in patients with severe cardiac damage. Our findings indicated the importance of regular antenatal care and treatment adherence in patients with hyperthyroidism. CONCLUSION: The timely and accurate diagnosis of HHD and the implementation of effective management are important for a better prognosis in pregnant women with HHD. Improvement in patients' awareness of thyrotoxicosis is needed.

New radiocarbon and archaeobotanical evidence reveal the timing and route of southward dispersal of rice farming in south China.

The origins and spreads of rice agriculture have been enduring topics, yet the timing and southward dispersal from the Yangtze River Basin have been difficult to trace, due to the scarcity of archaeobotanical data, especially systematic macro-plant remains examination, combined with the poor preservation in the humid climate and acidic soils of China's southern provinces. Here, we report new radiocarbon dating and preserved rice phytolith evidence, derived from three Late Neolithic archaeological sites in south China, dated about 5,000-4,100 cal a BP. Our results demonstrate that rice farming had spread southward through the mountainous regions of Wuyi and Nanling, then entered the areas of Western Fujian and North Guangdong by 5,000 cal a BP, followed by continued expansion into coastal areas of East China Sea and South China Sea, also crossing the Taiwan Strait, around 4,500-4,000 cal a BP. The North River, East River, Min River, and possibly other river systems likely were influential as pathways or conduits.